Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

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Brief Title

Ph II SAHA and Bevacizumab for Recurrent Malignant Glioma Patients

Official Title

Phase II Study of Bevacizumab and Vorinostat for Recurrent WHO Grade IV Malignant Glioma Patients

Brief Summary

      It has been shown that bevacizumab has significant anti-tumor activity in patients with
      recurrent glioblastoma multiforme. Vorinostat has modest anti-tumor activity against
      malignant glioma and can enhance the action of both chemotherapy and anti-angiogenics.
      Patients will be treated with a combination of bevacizumab and vorinostat.
    

Detailed Description

      There is no effective therapy for patients with recurrent glioblastoma multiforme (GBM) hence
      such patients remain a major unmet need in oncology. The investigators have recently
      demonstrated that bevacizumab (BV), a humanized monoclonal antibody against vascular
      endothelial growth factor, has significant anti-tumor activity among recurrent glioblastoma
      multiforme patients. Vorinostat has modest anti-tumor activity against malignant glioma and
      can potentiate the action of both chemotherapy and anti-angiogenics. The current study is
      designed to evaluate the anti-tumor activity of vorinostat when combined with BV among
      recurrent glioblastoma multiforme patients.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Six-month Progression-free Survival (PFS6)

Secondary Outcome

 Radiographic Response

Condition

Recurrent Glioblastoma Multiforme

Intervention

Vorinostat

Study Arms / Comparison Groups

 Vorinostat & Bevacizumab
Description:  Patients will be administered bevacizumab every 2 weeks and vorinostat will be taken on days 1-7 and 15-21 of each 28-day cycle at 400 mg per day.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

48

Start Date

January 2013

Completion Date

February 2016

Primary Completion Date

December 2014

Eligibility Criteria

        Inclusion Criteria:

          -  Age > 18 years.

          -  An interval of at least 4 weeks between prior surgical resection or one week from
             stereotactic biopsy.

          -  An interval of at least 12 weeks from the end of prior radiotherapy unless there is a
             new area of enhancement consistent with recurrent tumor outside of the radiation
             field, or there is biopsy-proven tumor progression

          -  An interval of at least 4 weeks from prior chemotherapy [6 weeks for nitrosoureas, 1
             week for daily administered chemotherapy (metronomic dosing)] or investigational agent
             unless the patient has recovered from all anticipated toxicities associated with that
             therapy.

          -  Eastern Cooperative Oncology Group (ECOG) 0-1.

          -  Hematocrit ≥ 29%, hemoglobin ≥ 9, absolute neutrophil ≥1,500 cells/microliter,
             platelets ≥ 100,000 cells/microliters.

          -  Serum creatinine, serum glutamic oxaloacetic transaminase(SGOT) and bilirubin < 1.5
             times upper limit of normal.

          -  Signed informed consent approved by the Institutional Review Board prior to patient
             entry.

          -  No evidence of hemorrhage on the baseline MRI or CT scan other than those that are
             stable grade 1.

          -  If sexually active, patients will take contraceptive measures for the duration of the
             treatments. Medically acceptable contraceptives include: (1) surgical sterilization
             (such as a tubal ligation, hysterectomy, vasectomy), (2) approved hormonal
             contraceptives (such as birth control pills, patches, implants or injections), (3)
             barrier methods (such as a condom or diaphragm) used with a spermicide, or (4) an
             intrauterine device (IUD).

        Exclusion Criteria:

        Disease-specific exclusions

          -  More than 2 prior episodes of disease progression

          -  Prior therapy with histone deacetylase inhibitors; valproic acid is not permitted and
             patients previously treated with valproic acid must be off valproic acid for at least
             30 days prior to initiation of study medication

          -  Prior bevacizumab therapy

          -  Co-medication that may interfere with study results; e.g. immuno-suppressive agents
             other than corticosteroids

          -  Active infection requiring intravenous antibiotics

          -  Severe hepatic insufficiency, active viral hepatitis or HIV infection

          -  Requires therapeutic anti-coagulation with warfarin

        General medical exclusions

        Subjects meeting the following criteria are ineligible for study entry:

          -  Inability to comply with study and/or follow-up procedures

        Bevacizumab-specific exclusions

          -  Inadequately controlled hypertension (defined as systolic blood pressure > 150 and/or
             diastolic blood pressure > 100 mmHg on antihypertensive medications)

          -  Any prior history of hypertensive crisis or hypertensive encephalopathy

          -  New York Heart Association (NYHA) Grade II or greater congestive heart failure (see
             Appendix E)

          -  History of myocardial infarction or unstable angina within 6 months prior to study
             enrollment

          -  History of stroke or transient ischemic attack within 6 months prior to study
             enrollment

          -  Significant vascular disease (e.g., aortic aneurysm, aortic dissection)

          -  Symptomatic peripheral vascular disease

          -  Evidence of bleeding diathesis or coagulopathy

          -  Major surgical procedure, open biopsy, or significant traumatic injury within 28 days
             prior to study enrollment or anticipation of need for major surgical procedure during
             the course of the study

          -  Core biopsy or other minor surgical procedure, excluding placement of a vascular
             access device, within 7 days prior to study enrollment

          -  History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess
             within 6 months prior to study enrollment

          -  Serious, non-healing wound, ulcer, or bone fracture

          -  Proteinuria at screening as demonstrated by either:

               -  Urine protein:creatinine (UPC) ratio >= 1.0 at screening OR

               -  Urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria
                  on dipstick urinalysis at baseline should undergo a 24 hour urine collection and
                  must demonstrate ≤ 1g of protein in 24 hours to be eligible).

          -  Known hypersensitivity to any component of bevacizumab

          -  Pregnant (positive pregnancy test) or lactating. Refuse the use of effective means of
             contraception (men and women) in subjects of child-bearing potential
      

Gender

All

Ages

18 Years - 120 Years

Accepts Healthy Volunteers

No

Contacts

Katherine Peters, MD, PhD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01738646

Organization ID

Pro00024983


Responsible Party

Sponsor

Study Sponsor

Duke University

Collaborators

 Genentech, Inc.

Study Sponsor

Katherine Peters, MD, PhD, Principal Investigator, Duke University


Verification Date

November 2016